Reaction mass of 2,2'-(Ethylenedioxy)diethanol and 3,6,9-Trioxaundecane-1,11-diol

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

Additional information is available in the endpoint summaries and the read-across justification (see section 13).

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Duration:

72 h

Dose descriptor:

NOEC

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: test result from RA Source CAS 4792-15-8 (Mead, 2003)

Duration:

8 d

Dose descriptor:

EC5

Effect conc.:

> 10 000

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: test result from RA Source CAS 112-27-6 (Bringmann & Kühn, 1978)

Duration:

8 d

Dose descriptor:

EC5

Effect conc.:

2 700 mg/L

Nominal / measured:

not specified

Conc. based on:

test mat.

Basis for effect:

not specified

Remarks on result:

other: test result from RA Source CAS 111-46-6 (Bringmann & Kühn, 1977/78)

Duration:

8 d

Dose descriptor:

EC5

Effect conc.:

> 10 000 mg/L

Nominal / measured:

not specified

Conc. based on:

test mat.

Basis for effect:

not specified

Remarks on result:

other: test result from RA Source CAS 107-21-1 (Bringmann & Kühn, 1977/78)

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

> 6 500 - < 13 000 mg/L

Nominal / measured:

not specified

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: test result from RA Source CAS 107-21-1 (DOW, 1982)

Reference 2

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

- QMRF: see 'Overall remarks, attachments'.
- QPRF: see 'Executive summary'.

Qualifier:

no guideline followed

Principles of method if other than guideline:

ECOSAR v1.11: Estimation of acute and chronic toxicity to green algae for chemical class "Neutral Organic SAR (Baseline Toxicity)"

GLP compliance:

no

Specific details on test material used for the study:

- SMILES Code: O(CCOCCO)CCO

Test organisms (species):

other: Green algae

Water media type:

freshwater

Total exposure duration:

96 h

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

20 518 mg/L

Nominal / measured:

estimated

Conc. based on:

act. ingr.

Basis for effect:

other: no data

Remarks on result:

other: ECOSAR chemical class: "Neutral Organic SAR (Baseline Toxicity)"

Remarks:

The substance is within the applicability domain of the model.

Dose descriptor:

other: Chronic Value (ChV)

Effect conc.:

2 486 mg/L

Nominal / measured:

estimated

Conc. based on:

act. ingr.

Basis for effect:

other: no data

Remarks on result:

other: ECOSAR chemical class: "Neutral Organic SAR (Baseline Toxicity)"

Remarks:

The substance is within the applicability domain of the model.

Executive summary:

QPRF: ECOSAR v1.11

1.	Substance	See “Test material identity”
2.	General information
2.1	Date of QPRF	See “Data Source (Reference)”
2.2	QPRF author and contact details	See “Data Source (Reference)”
3.	Prediction
3.1	Endpoint (OECD Principle 1)	Endpoint		Toxicity to aquatic organisms: -      Green algae: 96-h EC50 -      Green algae: chronic value
		Dependent variable		-      Green algae: 96-h EC50 -      Green algae: chronic value
3.2		Model or submodel name		ECOSAR – Chemical Class: Neutral Organics: -      Green algae: 96-h EC50 -      Green algae: chronic value
		Model version		1.11
		Reference to QMRF		QMRF: Estimation of Toxicity to Aquatic Organisms Using ECOSAR v1.11 (EPI Suite v4.11): Chemical Class: Neutral Organics: Green Algae 96-h EC50 and Chronic Value
		Predicted value (model result)		See “Results and discussion”
		Input for prediction		- For chemical identity: CAS number or SMILES - Log Kow (optionally entered by user, or estimated by KOWWIN v1.68)
		Descriptor values		See “Any other information on materials and methods incl. tables”
3.3	Algorithm (OECD Principle 2)	Domain: The complete training sets for ECOSAR’s estimation methodology are not available since some of the information is confidential; therefore, the description of a precise estimation domain for this methodology is not possible.
		The substance is an organic chemical with a molecular weight ≤ 1000 g/mol.			Fulfilled
		The substance is a member of the chemical class “Neutral Organics”.			Fulfilled
		In case the log Kow is estimated via KOWWIN v1.68: The substance is within the estimation domain of KOWWIN v1.68.			Fulfilled
3.4	The uncertainty of the prediction (OECD principle 4)	Neutral Organics:	Effect level		n	r^2
		Green algae	96-h EC50		41 + 9	0.6782
			chronic value		34 + 5	0.6971
3.5	The chemical mechanisms according to the model underpinning the predicted result (OECD principle 5)	The octanol/water partition coefficient (Kow) is the major physical-chemical attribute correlating a chemical structure to toxic effect for nonreactive neutral organic chemicals. The most frequently used relationship is the logarithm of the Kow value versus the median toxicity (LC50 and EC50) value. If the log Kow value exceeds a model specific value (acute: 6.4; chronic: 8.0), or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted. Members of the chemical class “Neutral Organics” act via simple nonpolar narcosis generally thought of as a reversible, drug-induced loss of conscience (general anesthesia) which is also referred to as baseline toxicity.

Estimation domain check - Green Algae 96-h EC50

Model:	ECOSAR v1.11, ECOSAR class: Neutral Organics
Test type:	Green Algae 96 -h EC50
Substance name:	Ethanol, 2,2 -[1,2-ethanediylbis(oxy)]bis-
CAS No.	112-27-6
SMILES	O(CCOCCO)CCO
Type	organic substance
Molecular weight	150.173 g/mol
Water solubility	1.00E+04 mg/L
Physical state	not solid
log Kow	-1.75
Substance type	Substance within applicability domain
Molecular weight	max. value: 1000 g/mol
	Substance within applicability domain
log Kow	Assessment regarding maximum values
	log Kow below maximum value.
Water solubility	Assessment regarding effects at saturation
	-

Estimation domain check - Green Algae ChV

Model:	ECOSAR v1.11, ECOSAR class: Neutral Organics
Test type:	Green Algae ChV
Substance name:	Ethanol, 2,2 -[1,2-ethanediylbis(oxy)]bis-
CAS No.	112-27-6
SMILES	O(CCOCCO)CCO
Type	organic substance
Molecular weight	150.173 g/mol
Water solubility	1.00E+04 mg/L
Physical state	not solid
log Kow	-1.75
Substance type	Substance within applicability domain
Molecular weight	max. value: 1000 g/mol
	Substance within applicability domain
log Kow	Assessment regarding maximum values
	log Kow below maximum value.
Water solubility	Assessment regarding effects at saturation
	-

References

- US EPA (2012). On-Line ECOSAR User’s Guide.

Reference 3

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

- QMRF: see 'Overall remarks, attachments'.
- QPRF: see 'Executive summary'.

Qualifier:

no guideline followed

Principles of method if other than guideline:

ECOSAR v1.11: Estimation of acute and chronic toxicity to green algae for chemical class "Neutral Organic SAR (Baseline Toxicity)"

GLP compliance:

no

Specific details on test material used for the study:

- SMILES Code: OCCOCCOCCOCCO

Test organisms (species):

other: Green algae

Water media type:

freshwater

Total exposure duration:

96 h

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

41 095 mg/L

Nominal / measured:

estimated

Conc. based on:

act. ingr.

Basis for effect:

other: no data

Remarks on result:

other: ECOSAR chemical class: "Neutral Organic SAR (Baseline Toxicity)"

Remarks:

The substance is within the applicability domain of the model.

Dose descriptor:

other: Chronic Value (ChV)

Effect conc.:

4 706 mg/L

Nominal / measured:

estimated

Conc. based on:

act. ingr.

Basis for effect:

other: no data

Remarks on result:

other: ECOSAR chemical class: "Neutral Organic SAR (Baseline Toxicity)"

Remarks:

The substance is within the applicability domain of the model.

Executive summary:

QPRF: ECOSAR v1.11

1.	Substance	See “Test material identity”
2.	General information
2.1	Date of QPRF	See “Data Source (Reference)”
2.2	QPRF author and contact details	See “Data Source (Reference)”
3.	Prediction
3.1	Endpoint (OECD Principle 1)	Endpoint		Toxicity to aquatic organisms: -      Green algae: 96-h EC50 -      Green algae: chronic value
		Dependent variable		-      Green algae: 96-h EC50 -      Green algae: chronic value
3.2		Model or submodel name		ECOSAR – Chemical Class: Neutral Organics: -      Green algae: 96-h EC50 -      Green algae: chronic value
		Model version		1.11
		Reference to QMRF		QMRF: Estimation of Toxicity to Aquatic Organisms Using ECOSAR v1.11 (EPI Suite v4.11): Chemical Class: Neutral Organics: Green Algae 96-h EC50 and Chronic Value
		Predicted value (model result)		See “Results and discussion”
		Input for prediction		- For chemical identity: CAS number or SMILES - Log Kow (optionally entered by user, or estimated by KOWWIN v1.68)
		Descriptor values		See “Any other information on materials and methods incl. tables”
3.3	Algorithm (OECD Principle 2)	Domain: The complete training sets for ECOSAR’s estimation methodology are not available since some of the information is confidential; therefore, the description of a precise estimation domain for this methodology is not possible.
		The substance is an organic chemical with a molecular weight ≤ 1000 g/mol.			Fulfilled
		The substance is a member of the chemical class “Neutral Organics”.			Fulfilled
		In case the log Kow is estimated via KOWWIN v1.68: The substance is within the estimation domain of KOWWIN v1.68.			Fulfilled
3.4	The uncertainty of the prediction (OECD principle 4)	Neutral Organics:	Effect level		n	r^2
		Green algae	96-h EC50		41 + 9	0.6782
			chronic value		34 + 5	0.6971
3.5	The chemical mechanisms according to the model underpinning the predicted result (OECD principle 5)	The octanol/water partition coefficient (Kow) is the major physical-chemical attribute correlating a chemical structure to toxic effect for nonreactive neutral organic chemicals. The most frequently used relationship is the logarithm of the Kow value versus the median toxicity (LC50 and EC50) value. If the log Kow value exceeds a model specific value (acute: 6.4; chronic: 8.0), or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted. Members of the chemical class “Neutral Organics” act via simple nonpolar narcosis generally thought of as a reversible, drug-induced loss of conscience (general anesthesia) which is also referred to as baseline toxicity.

Estimation domain check - Green Algae 96-h EC50

Model:	ECOSAR v1.11, ECOSAR class: Neutral Organics
Test type:	Green algae 96-h EC50
Substance name:	3,6,9-trioxaundecane-1,11-diol
CAS No.	112-60-7
SMILES	OCCOCCOCCOCCO
Type	organic substance
Molecular weight	194.23 g/mol
Water solubility	1.00E+06 mg/L
Physical state	not solid
log Kow	-2.02
Substance type	Substance within applicability domain
Molecular weight	max. value: 1000 g/mol
	Substance within applicability domain
log Kow	Assessment regarding maximum values
	log Kow below maximum value.
Water solubility	Assessment regarding effects at saturation
	-

Estimation domain check - Green Algae ChV

Model:	ECOSAR v1.11, ECOSAR class: Neutral Organics
Test type:	Green algae ChV
Substance name:	3,6,9-trioxaundecane-1,11-diol
CAS No.	112-60-7
SMILES	OCCOCCOCCOCCO
Type	organic substance
Molecular weight	194.23 g/mol
Water solubility	1.00E+06 mg/L
Physical state	not solid
log Kow	-2.02
Substance type	Substance within applicability domain
Molecular weight	max. value: 1000 g/mol
	Substance within applicability domain
log Kow	Assessment regarding maximum values
	log Kow below maximum value.
Water solubility	Assessment regarding effects at saturation
	-

References

- US EPA (2012). On-Line ECOSAR User’s Guide.

Description of key information

From the available test data in combination with QSAR calculations it can be concluded, that the reaction mass of 2,2'-(ethylenedioxy)diethanol 3,6,9-trioxaundecane-1,11-diol shows a very low toxicity to aquatic algae.

Additional information

The assessment on the toxicity to aquatic algae and cyanobacteria of the reaction mass of 2,2'-(ethylenedioxy)diethanol 3,6,9-trioxaundecane-1,11-diol is based on studies with main component triethylene glycol (CAS 112-27-6), close structural analogues ethylene glycol (CAS 107-21-1), diethylene glycol (CAS 111-46-6) and pentaethylene glycol (CAS 4792-15-8) and on QSAR-generated data (of the main components).

For structural analogue pentaethylene glycol, the toxicity towards freshwater algae was determined in a study according to OECD TG 201 (compliance with GLP criteria not specified) (Mead, 2003). In this study, exponentially growing freshwater algae (Pseudokirchneriella subcapitata) were exposed to nominal test substance concentrations of up to 100 mg/L in a limit test for 72 hours under static conditions. The 72-h NOEC value for growth rate is determined to be >100 mg/L.

For main component triethylene glycol and structural analogues ethylene glycol and diethylene glycol, 8 days cell growth inhibition tests with the green algae (Scenedesmus quadricauda) were conducted according to the method described by Bringmann & Kühn (1977/78). The reported toxic threshold concentrations, which are comparable with an EC5 value, ranged between 2700 mg/L for diethylene glycol and >10000 mg/L for ethylene glycol and triethylene glycol (based on growth rate). Furthermore, for ethylene glycol a further study with algae (Selenastrum capricornutum) is available, which was conducted according to EPA standards. After 96 hours of exposure an EC50 range value of 6500 - 13000 mg/L is reported (Dow, 1982).

Finally, the expected acute and long-term toxicity to green algae was calculated with the QSAR model ECOSAR v1.11 (EPISuite v.4.11). Based on the results of the estimations a very low chronic toxicity has to be expected. The calculated acute (EC50) and chronic value (ChV) are 20518 and 2482 mg/L for triethylene glycol and 41095 and 4706 mg/L for tetraethylene glycol, respectively (BASF, 2017).

Together, the available information provides sufficient evidence to conclude that the test substance shows a very low toxicity to aquatic algae and cyanobacteria. All data shows no toxicity is to be expected up to 100 mg/L (relevant cut-off value for CLP). As a worst-case approach, a NOEC (effect) value of 100 mg/L is used in the derivation of PNECs.

QSAR-disclaimer

In Article 13 of Regulation (EC) No 1907/2006, it is laid down that information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI (of the same Regulation) are met.

 

According to Annex XI of Regulation (EC) No 1907/2006 (Q)SAR results can be used if (1) the scientific validity of the (Q)SAR model has been established, (2) the substance falls within the applicability domain of the (Q)SAR model, (3) the results are adequate for the purpose of classification and labeling and/or risk assessment and (4) adequate and reliable documentation of the applied method is provided.

 

For the assessment ofReaction mass of 2,2'-(Ethylenedioxy)diethanol and 3,6,9-Trioxaundecane-1,11-diol,(Q)SAR results of its main constituents were used to assess toxicity to aquatic organisms.The criteria listed in Annex XI of Regulation (EC) No 1907/2006 are considered to be adequately fulfilled and therefore the endpoint(s) sufficiently covered and suitable for risk assessment.